重组伪狂犬病病毒的研究进展

PROGRESS ON RECOMBINANT PSEUDORABIES VIRUS VACCINES

伪狂犬病病毒(PRV)属于疱疹病毒,含有多个复制非必需区,可以通过基因缺失研制弱毒疫苗,也可以通过异源基因的插入或替换构建活载体疫苗。目前构建重组PRV的技术方法包括传统同源重组技术、细菌人工染色体技术(BAC)、CRISPR/Cas9介导的基因编辑技术。2011以来,一种毒力更强的变异株在我国暴发流行,应用变异株构建的基因缺失活疫苗(gE/gI、gE/TK或者TK/gE/gI)能对变异株提供完全的保护,为PRV在我国的净化和PRV变异株活载体疫苗的构建奠定了基础。研究发现以PRV基因缺失株为载体,与其他病原的抗原编码基因共同构建重组病毒,能快速地诱导细胞免疫和体液免疫,达到一针多防的效果,应用前景广阔。适合的插入位点选择、外源基因高效表达和克服PRV母源抗体干扰等是提高活载体效果的关键。

Pseudorabies viruses(PRV)belongs to the herpesvirus group.The virus has a 150 kb genome containing some nonessential regions that can be deleted to construct live attenuated PRV vaccines or replaced with genes encoding heterologous antigens to construct live vector vaccines.The strategy to generate recombinant PRV vaccines includes conventional homologous recombination,bacterial artificial chromosome(BAC)and CRISPR/Cas9-mediated gene editing.Since 2011,a novel virulent PRV variant has emerged in several pig herds in China.Gene deletion(gE/gI、gE/TK or TK/gE/gI)mutants of the emerging PRV has demonstrated complete protection against challenge by the virulent strain,which provided an effective method for the eradication of PRV in China and construction of PRV vector vaccine in China.Recombinant PRV vaccines based on gene deletions/insertions are able to express exogenous antigens and stimulate strong cellular and humoral immune responses against PRV infection.Nevertheless,suitable insertion sites,high level expression of heterologous gene and elimination of maternal antibody interference are critical for obtaining a highly efficacious vector vaccine.